Population-based nationwide incidence of complications after gastrectomy for gastric adenocarcinoma in Finland

Abstract Background The incidence of postoperative complications after gastrectomy for gastric cancer is not well known. More population-based studies using established complication classifications are needed for international comparison. The aim of this study was to evaluate the population-based incidence of postoperative complications after gastrectomy for gastric cancer. Methods This population-based study based on the Finnish National Esophago-Gastric Cancer Cohort included all patients at least 18 years of age undergoing gastrectomy for gastric adenocarcinoma in Finland during 2005–2016. The occurrence of complications 30 and 90 days after surgery was graded based on the Esophagectomy Complications Consensus Group definitions and the severity of complications was assessed using the Clavien–Dindo scale. Results This study included a total of 2196 patients. Postoperative complications occurred in 906 (41.3 per cent) of patients during 30 days after surgery and in 946 (43.1 per cent) during 90 days after surgery. Clavien–Dindo grade III or higher complications occurred in 375 (17.1 per cent) of patients. The most common complications 90 days after surgery by Esophagectomy Complications Consensus Group upper-level categories were gastrointestinal (n = 438; 19.9 per cent), including anastomotic leak, infectious (n = 377; 17.2 per cent) and pulmonary (n = 335; 15.3 per cent) complications. Postoperative mortality rate was occurred in 72 (3.3 per cent) patients within 30 days and in 161 (7.3 per cent) patients within 90 days after surgery. The median duration of postoperative hospital stay was 9 days (interquartile range 4–14). Conclusions Postoperative complications are common across all types of gastrectomy and the majority occur during the first 30 postoperative days. This study informs the patients and caregivers of the expected outcomes of gastrectomy.


Introduction
Gastric cancer is the third leading cause of cancer death worldwide 1 .The standard treatment for local or locally advanced gastric cancer is gastrectomy, which is associated with high mortality and morbidity rates, a long hospital stay and a high reoperation rate 2 .Population-based studies on postoperative complications of gastric cancer surgery from Western countries are sparse.In a previous Dutch study, the incidence of postoperative complications after gastrectomy was 43 per cent, while the 30-day mortality rate was 4.4 per cent and readmission occurred in 14 per cent of the patients 2 .A Japanese nationwide study of surgically resected gastric cancer resulted in a 30-day mortality rate of 0.5 per cent and 90-day mortality rate of 1.7 per cent after surgery 3 .
The severity of complications is commonly graded using the Clavien-Dindo classification for surgical complications based on the type of treatment needed 4 , but without differentiating between the types of complications.Previous nationwide analyses have been reported using the Esophagectomy Complications Consensus Group (ECCG) standardized list of complications 5 , providing a comparison point for a national analysis.

Original Article
The aim of the present study was to describe the population-based nationwide incidence of complications after gastrectomy for gastric adenocarcinoma in Finland according to the Clavien-Dindo and the ECCG classifications, grouped by the type of surgery and surgical approach.

Study design
This study was a population-based nationwide retrospective cohort study in Finland during 2005-2016, using the Finnish National Esophago-Gastric Cancer Cohort (FINEGO) 6 .All patients who underwent gastrectomy for gastric adenocarcinoma in Finland were included in this study.Patients who underwent another type of surgery other than gastrectomy (for example palliative gastric bypass), those with other histology than gastric adenocarcinoma or without a histological confirmation of cancer were excluded, as well as those without available data.

Data collection
All potentially eligible patients were identified from the Finnish cancer and patient registries 7,8 .Records of patients with gastric cancer or tumour diagnosis in the Finnish Cancer Registry or the Finnish Patient Registry and a relevant surgical code in the Patient Registry were retrieved from the respective hospitals and healthcare units and screened for eligibility by expert surgeons 9 .
The patient registry provided data on date of surgery, age, sex and co-morbidity.Cancer stage information was updated according to TNM 8th edition 10 .Following the ascertainment of eligibility, patient records, including surgical charts and pathology assessments, were evaluated by expert upper gastrointestinal surgeons, and information on tumour and treatment characteristics, as well as complications, was retrieved and input to the common database using the REDCap (Research Electronic Data Capture) web-based tool hosted at the University of Oulu, Finland 11,12 .Clavien-Dindo grade I complications were not collected, as the assessment of these complications was deemed unfeasible given the retrospective design, the low clinical relevance and subjectivity.Statistics Finland provided the reliable and 100 per cent complete mortality rate data 13 .

Outcomes
The primary outcome was occurrence of any postoperative complication during 30 and 90 days.Secondary outcomes were types of 30-day and 90-day complications grouped by the ECCG upper-level categories, the severity of the complications using the Clavien-Dindo classification 4 , reoperation rate, length of intensive care unit (ICU) stay, duration of hospital stay and in-hospital, 30-day or 90-day mortality rates.
Clavien-Dindo grades IIIa and higher were considered to be major complications.The consensus by the ECCG was used to separately evaluate each complication, and to group them in upper-level complication categories (pulmonary, cardiac, gastrointestinal, urologic, thromboembolic, neurological, infectious, wound and other) 5 as shown in Table S1.Reoperation rate was defined as surgical interventions performed in the operating theatre, including both with and without general anaesthesia.

Statistical methods
Statistical analysis was descriptive.The patient and tumour characteristics, complications, reoperation rate, length of postoperative ICU stay, duration of hospital stay, and mortality rate are presented as frequencies and percentages.Complications are also reported for total and distal gastrectomy, open and laparoscopic surgery, as well as curative and palliative gastrectomy.IBM SPSS version 27 (Armonk, NY, USA) was used for data management and analysis.

Patients
From 2005 to 2016, a total of 2708 patients were identified from the national registries and assessed for eligibility; of those, a total of 2196 patients were included in the analysis (Fig. 1).The majority were males (n = 1227; 55.9 per cent) with a median age of 71 years at the time of surgery, with no co-morbidity (n = 1104; 50. 3  Postoperative complication rates according to surgical approach, resection type and curative versus palliative-intent gastrectomy are reported in Tables 3, 4, and 5 respectively.

Discussion
This Finnish population-based nationwide study presents the incidence of 30-and 90-day morbidity rate after gastrectomy, as well as those of laparoscopic-and open-, total-and distal-as well as curative-intended and palliative gastrectomy.The most common categories of complications were gastrointestinal, followed by infectious, pulmonary and thromboembolic complications.
The 2019 Gastrectomy Complications Consensus Group (GCCG) 14 classified major specific complications after gastrectomy, and it could be argued that it is the preferable method to report complications.The GCCG list was published when the FINEGO data collection was on-going, and items between the GCCG and ECCG lists were relatively similar, so the ECCG list could also be considered a valid classification method.
A recent population-based national study on the occurrence of complications after gastrectomy for gastric cancer using the ECCG classification was based on the Dutch DUCA database  (study number population = 928) 2 and it found a complication rate of 43 per cent.The 30-day complication rate in the present study was 41.3 per cent.The occurrence of major complications was quite similar (19 per cent versus 17.1 per cent).The most common complications grouped by the ECCG in the Dutch study were gastrointestinal (18 per cent), pulmonary (17 per cent) and infectious (9 per cent), while in this study they were infectious (16.2 per cent), gastrointestinal (16.1 per cent) and pulmonary (14.9 per cent) complications.The infectious complication rate was higher in the present study and could be due to the early administration of antibiotic therapy in the past without a clear infectious focus.A European retrospective observational study (n = 1349) from high-volume hospitals using the GCCG classification estimated the overall incidence of complications, 90 days after surgery, at 29.8 per cent, the most common complications being non-surgical infections (23 per cent), anastomotic leak (9.8 per cent) and other postoperative abnormal fluid from drainage and/or abdominal collections (9.3 per cent) 15 .The lower incidence of complications in that study could be explained by the stricter criteria in the GCCG classification.Thirty-day mortality rates were similar (3.3 per cent versus 3.6 per cent) between the studies, but 90-day mortality rates were slightly higher in the present study (7.3 per cent versus 4.3 per cent), due to the inclusion of patients who underwent a palliative gastrectomy.
A Dutch population-based study found fewer wound complications and a shorter duration of hospital stay after laparoscopic compared with open gastrectomy 16 .Laparoscopic distal gastrectomy was also associated with lower overall and wound complications compared with open gastrectomy in a Korean study 17 .In the present study, results were relatively similar, but there was a lower 90-day mortality rate in the laparoscopic gastrectomy group.Patients who underwent laparoscopic surgery had less advanced disease due to the learning curve of laparoscopic gastrectomy in many centres.
For total and distal gastrectomy, a population-based Dutch study found that the most common complications after total or subtotal gastric cancer surgery were pulmonary (15 per cent), anastomotic leakage (7 per cent) and cardiac (6 per cent) complications 18 .In the present study the incidence of complications was similar between total and distal gastrectomy.Observational studies have suggested better survival with palliative gastrectomy in advanced gastric cancer compared with conservative treatment 19,20 , but this hypothesis was not  supported by the results of the Japanese randomized REGATTA trial 21 .In the present study, similar 90-day complications after palliative-and curative-intended gastrectomy were observed, but there were longer durations of hospital stay, more major complications, and a much higher 90-day mortality rate after palliative-versus curative-intended gastrectomy, probably due to the weaker state of health of these patients.Occurrence of a complication could impair health-related quality of life of patients in the long term 22 .As a population-based nationwide study, this study informed the caregivers and patients of the incidence of complications after gastrectomy for gastric cancer.Furthermore, the incidence of complications with typical surgical approaches, surgery types and curative and palliative intent were described, facilitating patient-caregiver discussions, and providing realistic information in specific settings and circumstances.
The strengths of this study include the inclusion of a large population, allowing accurate estimates and reducing selection bias, and the ascertainment of complications by expert surgeons improved the quality of data.
Limitations were due to its retrospective nature, and the possible lack of data that could not be retrieved.Some categories, such as laparoscopic and palliative surgery groups, had a relatively small number of patients, but the distributions of complications were relatively similar across different groups.Nevertheless, strict conclusions from the subcategories of gastric cancer surgery should be avoided.The proportion of patients receiving preoperative neoadjuvant therapy was only 14.8 per cent, which may limit the generalizability of the results in these patients.

Table 4 Postoperative complications after total and distal gastrectomy for gastric cancer during 2005-2016 according to ECCG Annals of Surgery 2015 5
ECCG, Esophagectomy Complications Consensus Group; ICU, intensive care unit; i.q.r., interquartile range.*In-hospital mortality.